A novel candidate hepatitis C virus genotype 4 subtype identified by next generation sequencing full-genome characterization in a patient from Saudi Arabia.

Background and aim: Hepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C. Methods: We analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing. Results: Our phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV. Conclusion: This discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles.

Corrigendum: Serum IgG antibodies from pregnant women reacting to mimotopes of Simian virus 40 large T antigen, the viral oncoprotein.

[This corrects the article DOI: 10.3389/fimmu.2017.00411.].

Serum IgG Antibodies from Pregnant Women Reacting to Mimotopes of Simian Virus 40 Large T Antigen, the Viral Oncoprotein.

Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens. Serum samples were collected from pregnant and non-pregnant women, with the same mean age. Women were in the range of 15-48 years old. Samples were assayed by an indirect ELISA employing specific SV40 LT mimotopes as antigens, whereas functional analysis was performed by neutralization of the viral infectivity in cell cultures. As a control, sera were analyzed for Ab against BK polyomavirus (BKPyV), which is a human polyomavirus homologous to SV40. Statistical analyses employed chi-square with Yates' correction, and Student's t tests. Indirect ELISAs indicated that pregnant women tested SV40 LT-positive with a prevalence of 17% (23/134), whereas non-pregnant women had a prevalence of 20% (36/180) (P > 0.05). Ab against BKPyV were detected with a prevalence of 80% in pregnant women and with a prevalence of 78% in non-pregnant women. These data indicate that SV40 infects at a low prevalence pregnant women. We may speculate that SV40, or a close human polyomavirus still undetected, could be transmitted from mother to fetus.

In vitro and in vivo human herpesvirus 8 infection of placenta.

Herpesvirus infection of placenta may be harmful in pregnancy leading to disorders in fetal growth, premature delivery, miscarriage, or major congenital abnormalities. Although a correlation between human herpesvirus 8 (HHV-8) infection and abortion or low birth weight in children has been suggested, and rare cases of in utero or perinatal HHV-8 transmission have been documented, no direct evidence of HHV-8 infection of placenta has yet been reported. The aim of this study was to evaluate the in vitro and in vivo susceptibility of placental cells to HHV-8 infection. Short-term infection assays were performed on placental chorionic villi isolated from term placentae. Qualitative and quantitative HHV-8 detection were performed by PCR and real-time PCR, and HHV-8 proteins were analyzed by immunohistochemistry. Term placenta samples from HHV-8-seropositive women were analyzed for the presence of HHV-8 DNA and antigens. In vitro infected histocultures showed increasing amounts of HHV-8 DNA in tissues and supernatants; cyto- and syncitiotrophoblasts, as well as endothelial cells, expressed latent and lytic viral antigens. Increased apoptotic phenomena were visualized by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method in infected histocultures. Ex vivo, HHV-8 DNA and a latent viral antigen were detected in placenta samples from HHV-8-seropositive women. These findings demonstrate that HHV-8, like other human herpesviruses, may infect placental cells in vitro and in vivo, thus providing evidence that this phenomenon might influence vertical transmission and pregnancy outcome in HHV-8-infected women.

Mutational patterns of paired blood and rectal biopsies in HIV-infected patients on HAART.

Blood and concurrent rectal biopsy samples of human immunodeficiency virus type 1 (HIV-1)-positive highly active antiretroviral therapy (HAART)-treated patients were tested for genotypic resistance by direct sequencing of reverse transcriptase (RT) and protease (PR) regions to compare the patterns of resistance in these compartments. Fourteen subjects (five with undetectable plasma viral load (pVL) and nine persistently viremic) were studied. Four of five patients with undetectable pVL also had undetectable mucosal HIV RNA; sequence analyses from proviral DNA (PBMCs and rectal biopsy) were obtained with none or few resistance-associated mutations and no alteration of susceptibility profile. All viremic patients, and one with negative pVL, had detectable levels of mucosal HIV RNA (1.93-4.21 log(10) copies/mg); sequences of HIV RNA (plasma and/or rectal biopsy) were also obtained, and multiple mutations generally compatible with current/past medications were detected. Overall, 40 HIV-1 PR and 42 RT sequences were analyzed, yielding a total of 42 PR and 47 RT sequence pairs (plasma/tissue-RNA; plasma-RNA/tissue-DNA; PBMC/tissue-DNA; tissue-DNA/RNA; tissue-RNA/PBMC-DNA; PBMC-DNA/plasma-RNA), which almost always differed at the total amino acid level (median percentage discordance 8.08% in the PR, 4.8% in RT). The median percentage of resistance position discordance equaled 88.8% (IQR = 20-100) in the PR and 74.55% (IQR = 31.75-100%) in the RT pairs, respectively. Different resistance levels were detected by means of a computer-assisted interpretation of mutational profiles. The results support the multiform evolution of HIV genotype in various body compartments and emphasize the participation of intestinal mucosa in HIV genotype selection. Samples from diverse tissues should be used for resistance evaluation to obtain a complete picture of drug resistance for antiretroviral-treated patients.